The long-term objective of this application is to identify differences in growth regulation between neoplastic and nonneoplastic cells that can be exploited in improving chemotherapy in man. Our first goal is to determine whether increases in the concentration of free intracellular calcium are important in growth regulation of neoplastic and nonneoplastic cells. Our specific aims include: (1)\determining whether an intracellular microinjection of calcium can produce events leading toward DNA synthesis, and (2)\using the introduction of Aequorin and Quin 2 into cells to determine whether growth factors do indeed produce an increase in the concentration of free intracellular calcium. We will monitor changes in centriole events by indirect immunofluorescence using anti-tubulin antibody and by electron microscopy. DNA synthesis will be followed by autoradiography using tritiated thymidine. Eventually these projects will allow us to ask how the role of intracellular calcium is different in the growth of nonneoplastic (3T3) and neoplastic cells (SV3T3 or 3T12). (J)